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Gadolinium Contrast Medium (MRI Contrast agents)

Authors: Dr Nick Ferris* Prof Stacy Goergen *

What are the generally accepted indications for a gadolinium contrast medium injection?

The gadolinium contrast agent increases the signal from tissues where there is increased blood flow, particularly in the setting of inflammation or neoplasm. The resulting improvement in contrast between normal and pathological tissue is often much higher than can be achieved with iodinated contrast at computed tomography (CT).

This is most useful in the brain and spinal cord, where the blood–brain barrier might be disrupted by the pathology, and the signal increase is therefore particularly strong.

It is also useful in suspected inflammatory joint disease, inflammatory bowel disease, and inflammatory and neoplastic conditions of solid organs, such as the liver and kidney. It is sometimes useful in inflammatory and neoplastic conditions of bone, muscle, and connective tissue.

A second category of uses exploits the greatly increased signal from blood vessels themselves, to allow the production of MR angiograms. This works best in the arterial phase of the contrast injection, meaning the scan must be completed very quickly (2–3 minutes). This technique (‘contrast-enhanced MRA’) is used outside the head; intracranially, slower non-gadolinium techniques produce better resolved images of the intracranial circulation.

What are the prerequisites for having a gadolinium contrast medium injection done?

patients with severe renal disease (eGFR <30 mL/min/1.73 m,2), or acutely deteriorating renal function, who would be at risk of nephrogenic systemic fibrosis;

patients who are, or might be, pregnant.

Hence, a history of any previous gadolinium-based contrast agent exposure, risk factors for, or known, kidney disease, and possible pregnancy, should be sought.

The RANZCR, in conjunction with the Australian and New Zealand Society of Nephrology and Kidney Health Australia, has issued guidelines on the use of gadolinium-containing MRI contrast agents in patients with renal impairment, endorsed in June 2013. Further information can be found in Diagnostic Imaging Pathways: Gadolinium based contrast medium.

If the answer to any of these questions is “yes”, an estimated glomerular filtration rate (eGFR) that has been carried out no more than 3 months before the examination should be available when the patient presents for the MRI.

Note that patients with chronic liver function impairment might have reduced muscle mass. This can make estimation of eGFR less accurate.

Pregnancy: the administration of contrast to a pregnant patient will be at the discretion of the supervising radiologist after consultation with the referring specialist, based on a risk–benefit assessment. Where there is uncertainty about pregnancy status, and gadolinium injection is deemed critical to the quality of the MRI examination, a pregnancy test (serum beta human chorionic gonadotropin (hCG)) should be obtained to guide the risk assessment.

Breast-feeding is not a contraindication to gadolinium administration (there is minimal excretion into breast milk, at levels much less than are allowed for intravenous doses in neonatal MRI). There is no requirement to express breast milk or withhold breast-feeding.

What are the adverse effects of a gadolinium contrast medium injection?

At the time of the scan:

Headache, nausea and dizziness in 1–4% of patients. These symptoms are transient and require no specific treatment.

Delayed (days to weeks):

Nephrogenic systemic fibrosis: this adverse effect has been seen in patients with severe renal failure, including cases in Australia. However, since the risk was recognised and effective screening measures put in place several years ago, there have been almost no new cases worldwide.
This condition is rare and, so far, has occurred only in people with severe kidney disease. No cases were reported before 1997. It causes swelling and tightening of the skin of the arms and legs, and less often the body. It develops over days to weeks, and can reduce movement of the joints. It can also cause damage to internal organs in rare cases. Approximately 5% of people with the most severe level of kidney function reduction will develop NSF after a gadolinium injection, and less than 5% of these people (or 3 in every 10,000 people with severely reduced kidney function) will die of it. The risk of NSF is much more common with some gadolinium contrast agents than others, and is more common after a patients has had multiple doses of gadolinium-based contrast media. It is not seen in people with normal kidney function who have gadolinium.

Improvements in kidney function, through kidney transplant or other measures, have been shown in some cases to result in remission of NSF, but this is not always the case. Certain medical conditions and procedures can increase the risk of NSF in patients with kidney function impairment and these include: vascular procedures (e.g. dialysis fistula revision, angioplasty), those with thrombotic tendency (for example, deep venous thrombosis) and those with recent onset of acute kidney failure (including transplant failure) in the weeks before developing NSF.

The risk of NSF needs to be seen in the context of how rare it is. On 8 June 2006, the American Food and Drug Administration (FDA) issued a public health advisory indicating that 25 patients who had received a gadolinium compound (Omniscan (gadodiamide)) had developed NSF. All of these patients had kidney failure, and of the 25 cases (which were reported by the Danish Medicines Agency), 20 were in Denmark and 5 in Austria. An updated warning from the FDA was issued in May 2007, and confirmed cases of NSF in patients receiving other gadolinium compounds (Omniscan, Magnevist (gadopentetate dimeglumine) and Optimark (gadoversetamide)).

Patients at greatest risk were again identified as those with acute or chronic kidney impairment, and the risk increased for patients who had received multiple doses of gadolinium compounds.

It appears that the contrast agents, Gadovist (Bayer Schering Pharma) Dotarem (Guerbet) and Prohance, are associated with a much lower chance of NSF even in patients with poor kidney function, so these are often used when it is felt that gadolinium administration is essential for diagnosis in patients with very poor kidney function. An example of this might be in a patient with cancer and neurological symptoms who needs a brain MRI to search for spread of the tumour, but who also has very poor kidney function. The use of gadolinium contrast in this situation makes it much easier in many cases for the radiologist to see evidence of early metastatic disease; that is, where the cancer has spread from the original tumour to another part of the body. One of the contrast media listed above, that are known to be much lower risk in terms of causing NSF, might be used in this situation after explaining the risk versus benefit to the patient.

Is there any specific post procedural care required following a gadolinium contrast medium injection?

Only for the more severe adverse effects listed above.

Are there alternative imaging tests, interventions or surgical procedures to a gadolinium contrast medium injection?

The total number of patients in whom there is a relative or absolute contraindication to the use of gadolinium contrast agents is small.

Contrast enhancement can also be achieved in CT and ultrasound, with the use of different agents. The choice of modality will depend on the anatomy to be assessed and the nature of the clinical problem.

In cardiac MRI, gadolinium-based contrast agents might be essential in assessing cardiac function and muscle viability. However, in ischaemic heart disease, numerous other modalities are available, such as conventional electrocardiogram stress testing, stress echo and thallium perfusion scanning, as well as transoesophageal echo. In the diagnosis of myocardial disease, such as specific types of cardiomyopathy, contrast-enhanced MRI might add to confidence in a particular diagnosis, but is rarely if ever essential for management.

Further information about gadolinium contrast medium

In high-risk groups (eGFR<30 mL/min/1.73 m2), or individuals with acutely unstable/deteriorating renal function, the risk–benefit of contrast-enhanced MRI will need to be assessed in conjunction with the radiologist. A history of previous exposure to gadolinium-based contrast agents or of other factors thought to contribute to the risk of NSF, such as metabolic acidosis, vascular surgery and recent thrombotic events, should be taken into account (see Contrast Medium: Gadolinium versus Iodine in patients with kidney problems).

Informed and written consent should be obtained from the high-risk group (or parents/guardians) by the MRI practice.

The gadolinium dose will be limited to standard doses (or less), limiting the ability to carry out contrast-enhanced MR angiograms.

In patients already receiving haemodialysis, in whom a gadolinium injection is deemed diagnostically essential, schedule gadolinium-based contrast agent administration immediately before haemodialysis and consider an extra dialysis session afterwards. Referring doctors should ensure that they discuss appropriate timing of the MRI scan with the MRI facility.

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